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使用DARTS技术鉴定癫痫小鼠大脑中的姜黄素靶点。

Identification of Curcumin Targets in the Brain of Epileptic Mice Using DARTS.

作者信息

Zhang Ninan, Lin Ruifan, Xu Honglin, Jing Xianghong, Zhou Hongwei, Wen Xiaoxiao, Xie Qi

机构信息

Institute of Acupuncture and Moxibustion, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

出版信息

ACS Omega. 2024 May 16;9(21):22754-22763. doi: 10.1021/acsomega.4c00825. eCollection 2024 May 28.

Abstract

Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin's ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin's role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.

摘要

姜黄素是一种从姜黄中提取的化合物,在东亚医学中传统上用于治疗包括癫痫在内的各种健康状况。尽管姜黄素参与了众多细胞信号通路,但其在癫痫治疗中的具体机制和靶点仍不清楚。我们的研究重点是确定姜黄素在癫痫小鼠大脑中的主要靶点和功能途径。使用药物亲和反应靶点稳定化(DARTS)和亲和色谱法,我们在小鼠大脑中确定了关键靶点,分别揭示了232个和70个潜在的姜黄素靶点。生物信息学分析表明,这些蛋白质与粘着斑和细胞骨架成分密切相关。使用DARTS进行的进一步实验,以及免疫荧光染色和细胞迁移试验,证实了姜黄素调节粘着斑动态和影响细胞迁移的能力。这项研究不仅推进了我们对姜黄素在癫痫治疗中作用的理解,也为识别神经疾病的治疗靶点提供了一个模型。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/209a/11137688/38bcbf5fcc23/ao4c00825_0001.jpg

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